Hydrogen Sulfide Inhibits High-Salt Diet-Induced Myocardial Oxidative Stress and Myocardial Hypertrophy in Dahl Rats.

The study aimed to examine the protective effect of hydrogen sulfide (H2S) on high-salt-induced oxidative stress and myocardial hypertrophy in salt-sensitive (Dahl) rats. Thirty male Dahl rats and 40 SD rats were included in the study. They were randomly divided into Dahl control (Dahl + NS), Dahl high salt (Dahl + HS), Dahl + HS + NaHS, SD + NS, SD + HS, SD + HS + NaHS, and SD + HS + hydroxylamine (HA). Rats in Dahl + NS and SD + NS groups were given chow with 0.5% NaCl and 0.9% normal saline intraperitoneally daily. Myocardial structure, α-myosin heavy chain (α-MHC) and ß-myosin heavy chain (ß-MHC) expressions were determined. Endogenous myocardial H2S pathway and oxidative stress in myocardial tissues were tested. Myocardial H2S pathway was downregulated with myocardial hypertrophy featured by increased heart weight/body weight and cardiomyocytes cross-sectional area, decreased α-MHC and increased ß-MHC expressions in Dahl rats with high-salt diet (all P < 0.01), and oxidative stress in myocardial tissues was significantly activated, demonstrated by the increased contents of hydroxyl radical, malondialdehyde and oxidized glutathione and decreased total antioxidant capacity, carbon monoxide, catalase, glutathione, glutathione peroxidase, superoxide dismutase (SOD) activities and decreased SOD1 and SOD2 protein expressions (P < 0.05, P < 0.01). However, H2S reduced myocardial hypertrophy with decreased heart weight/body weight and cardiomyocytes cross-sectional area, increased α-MHC, decreased ß-MHC expressions and inhibited oxidative stress in myocardial tissues of Dahl rats with high-salt diet. However, no significant difference was found in H2S pathway, myocardial structure, α-MHC and ß-MHC protein and oxidative status in myocardial tissues among SD + NS, SD + HS, and SD + HS + NaHS groups. HA, an inhibitor of cystathionine ß-synthase, inhibited myocardial H2S pathway (P < 0.01), and stimulated myocardial hypertrophy and oxidative stress in SD rats with high-salt diet. Hence, H2S inhibited myocardial hypertrophy in high salt-stimulated Dahl rats in association with the enhancement of antioxidant capacity, thereby inhibiting oxidative stress in myocardial tissues.

Hydrogen Sulfide Inhibits High-Salt Diet-Induced Renal Oxidative Stress and Kidney Injury in Dahl Rats.

BACKGROUND. The study was designed to investigate if H2S could inhibit high-salt diet-induced renal excessive oxidative stress and kidney injury in Dahl rats. METHODS. Male salt-sensitive Dahl and SD rats were used. Blood pressure (BP), serum creatinine, urea, creatinine clearance rate, and 24-hour urine protein were measured. Renal ultra- and microstructures were observed. Collagen-I and -III contents the oxidants and antioxidants levels in renal tissue were detected. Keap1/Nrf2 association and Keap1 s-sulfhydration were detected. RESULTS. After 8 weeks of high-salt diet, BP was significantly increased, renal function and structure were impaired, and collagen deposition was abundant in renal tissues with increased renal MPO activity, H2O2, MDA, GSSG, and (•)OH contents, reduced renal T-AOC and GSH contents, CAT, GSH-PX and SOD activity, and SOD expressions in Dahl rats. Furthermore, endogenous H2S in renal tissues was decreased in Dahl rats. H2S donor, however, decreased BP, improved renal function and structure, and inhibited collagen excessive deposition in kidney, in association with increased antioxidative activity and reduced oxidative stress in renal tissues. H2S activated Nrf2 by inducing Keap1 s-sulfhydration and subsequent Keap1/Nrf2 disassociation. CONCLUSIONS. H2S protected against high-salt diet-induced renal injury associated with enhanced antioxidant capacity and inhibited renal oxidative stress.

Endogenous sulfur dioxide alleviates collagen remodeling via inhibiting TGF-ß/Smad pathway in vascular smooth muscle cells.

The study was designed to investigate the role of endogenous sulfur dioxide (SO2) in collagen remodeling and its mechanisms in vascular smooth muscle cells (VSMCs). Overexpression of endogenous SO2 synthase aspartate aminotransferase (AAT) 1 or 2 increased SO2 levels and inhibited collagen I and III expressions induced by transforming growth factor (TGF)-ß1 in VSMCs. In contrast, AAT1 or AAT2 knockdown induced a severe collagen deposition in TGF-ß1-treated VSMCs. Furthermore, AAT1 or AAT2 overexpression suppressed procollagen I and III mRNA, upregulated matrix metalloproteinase (MMP)-13 expression, downregulated tissue inhibitors of MMP-1 level, and vice versa. Mechanistically, AAT1 or AAT2 overexpression inhibited phosphorylation of type I TGF-ß receptor (TßRI) and Smad2/3 in TGF-ß1-stimulated VSMCs. Whereas SB431542, an inhibitor of TGF-ß1/Smad signaling pathway, attenuated excessive collagen deposition induced by AAT knockdown. Most importantly, ectopically expressing AAT or exogenous addition of 100 µM SO2 blocked AAT deficiency-aggravated collagen accumulation in TGF-ß1-stimulatd VSMCs, while no inhibition was observed at 100 µM ethyl pyruvate. These findings indicated that endogenous SO2 alleviated collagen remodeling by controlling TGF-ß1/TßRI/Smad2/3-mediated modulation of collagen synthesis and degradation.